Much previous research has supported the idea that the uptake of oxygen by human erythrocytes (RBC's) in the lung is limited by the diffusion resistance of the RBC membrane to oxygen and that intracellular diffusion of oxygen and the rate of reaction of oxygen with hemoglobin are not rate-limiting. Other experiments, however, lead to the conclusion that the plasma membrane of the red cell is so permeable to oxygen that it should not limit the rate of oxygen uptake at all. An effectively unstirred layer of plasma surrounding the red blood cell is another factor that might partly limit the rate of oxygen uptake by the cell. While the role of the unstirred layer has been given little attention, there is experimental work that supports the idea that even in the extremely turbulent flow that exists in the rapid reaction apparatus there is an effective unstirred layer around the red cell of such dimensions that it might be expected to partly limit the rate of oxygen uptake. The aim of this project is to precisely define the role of the red cell plasma membrane and the influence of the unstirred layer on the kinetics of oxygen uptake by the human erythrocyte. In working toward this goal we will (1) determine the steady-state resistance to oxygen uptake by red cell ghosts located with an oxygen-consuming enzyme system under conditions that permit quantitation of the effect of the unstirred layer, (2) estimate the effect of the unstirred layer on the kinetics of oxygen uptake in the rapid reaction apparatus, (3) investigate the effect of in vivo and in vitro alterations in the size, shape, and deformability of erythrocytes on the effective thickness of the unstirred layer, and (4) investigate the effect of altered fludity of the erythrocyte plasma membrane on its permeability to oxygen. By coming to grips with the influences of the red cell membrane and the unstirred layer on the kinetics of oxygen uptake, we will contribute to enhanced understanding of the respiratory function of the human erythrocyte in health and disease.